Baseline Physical Activity Guideline Attainment and Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages

Q: What are the key findings of this study?

Baseline physical activity guideline attainment was associated with lower all-cause mortality overall (HR 0.774, 95% CI 0.675-0.888) across CKM stages 1 to 4.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular-kidney-metabolic (CKM) syndrome stages 1 to 4 (n=19654). Intervention: Baseline physical activity guideline attainment (≥150 min/week moderate-intensity, ≥75 min/week vigorous-intensity, or equivalent combination) vs. Not meeting baseline physical activity guidelines. Primary outcome: All-cause mortality (HR 0.774, 95% CI 0.675-0.888, p=.043 for interaction across CKM stages).

Xi Luo; Yanhua Wang; Wei Zhou; Feng Yu; Junbo Sun; Kefa Xiang; Fuming Wang; Zhijun Yuan; Jiahui Bao; Shuai Zhang; 郑毅敏; Feng Wu

doi:10.64898/2026.10.28.26366776

October 31, 2026Open Access

Baseline Physical Activity Guideline Attainment and Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages

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Key result

Meeting physical activity guidelines is linked to ~23% lower all-cause mortality across CKM stages.

HR 0.774
95% CI 0.675-0.888
P=.043 for interaction across CKM stages
n=19,654

Why the study?

Is baseline attainment of physical activity guidelines associated with lower all-cause and cardiovascular mortality across stages 1 to 4 of cardiovascular-kidney-metabolic (CKM) syndrome in US adults?

Key Points

To evaluate the association between meeting baseline physical activity guidelines and mortality across stages 1 to 4 of cardiovascular-kidney-metabolic (CKM) syndrome.
Target-trial emulation analyzing 19,654 adults aged 20 to 79 years with CKM stages 1 to 4 and eGFR ≥15 mL/min/1.73 m² from NHANES 2007–2018 linked to the National Death Index through 2019.
Participants were classified at baseline as meeting or not meeting physical activity guidelines, using within-stage propensity-score weighting in Cox models to assess all-cause and cardiovascular mortality.
Over 134,037 person-years and 1,190 deaths, baseline guideline attainment was associated with lower all-cause mortality overall (HR, 0.774; 95% CI, 0.675–0.888), with stage-specific HRs of 1.030 (95% CI, 0.779–1.361) at stage 1, 0.803 (0.565–1.142) at stage 2, 0.642 (0.491–0.840) at stage 3, and 0.727 (0.563–0.939) at stage 4 (P=0.043 for interaction).
Five-year absolute risk differences were +0.040, −0.830, −1.790, and −3.840 percentage points across stages 1 to 4, with only stage 4 excluding the null (95% CI, −7.200 to −0.590 percentage points).
Guideline attainment was similarly associated with reduced cardiovascular mortality overall (HR, 0.707; 95% CI, 0.547–0.914; 358 deaths).

Study Design

Type

Cohort (n=19,654)

Multicenter

Yes

Structured PICO

Is baseline attainment of physical activity guidelines associated with lower all-cause and cardiovascular mortality across stages 1 to 4 of cardiovascular-kidney-metabolic (CKM) syndrome in US adults?

P

Population

19,654 US adults aged 20-79 years with CKM syndrome stages 1-4 (mean age 48.3 years, 50.8% female), eGFR ≥15 mL/min/1.73 m², and no cancer history, followed for a median of 6.7 years (134,037 person-years).

E

Exposure

Baseline physical activity guideline attainment, defined as self-reported ≥150 minutes/week of moderate-intensity activity, ≥75 minutes/week of vigorous-intensity activity, or an equivalent combination (vigorous minutes counted double) across leisure time, work, and transportation (n=10,431 [53.1%]).

C

Comparator

Baseline physical activity guideline nonattainment (<150 minutes/week of moderate-equivalent physical activity at baseline), compared using within-stage stabilized inverse probability of treatment weights.

O

Outcome

All-cause mortality ascertained via probabilistic linkage to the National Death Index through December 31, 2019 (median follow-up 6.7 years; 5-year primary reading window for absolute risk differences).hard clinical

Main Result

Hazard Ratio: 0.774 (95% CI 0.675–0.888)

Absolute Risk Reduction: 1.74%

p-value: p=.043 for interaction across CKM stages

Limitations

Physical activity was measured once at baseline by self-report and does not capture sustained adherence
Observational study design (target-trial emulation) without randomized assignment, leaving potential for residual confounding and exposure misclassification
CKM stage 3 relied on high-risk metabolic and kidney features because NHANES did not ascertain subclinical cardiovascular disease
Ten-year absolute risk differences required extrapolation beyond administrative censoring for most participants
Negative control outcome analysis had few events (35 deaths) and imprecise estimates
Activity was measured once by self-report and groups were observed rather than randomized
Residual confounding and exposure misclassification remain possible
CKM stage 3 used a study-specific operational definition based on high-risk metabolic and kidney features because NHANES did not ascertain subclinical cardiovascular disease
Ten-year absolute risk estimates required extrapolation beyond administrative censoring for 65% of participants
The negative control outcome (unintentional injury death) had only 35 events and its estimate was too imprecise to calibrate residual confounding

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Implication

In US adults with CKM syndrome, meeting baseline physical activity guidelines is associated with lower overall all-cause and cardiovascular mortality, with the largest 5-year absolute risk reduction observed in stage 4 disease (-3.84 percentage points).

Abstract

Background The 2023 American Heart Association cardiovascular-kidney-metabolic (CKM) staging framework supports risk stratification, but evidence on guideline-level physical activity across stages remains limited. Methods We emulated a target-trial protocol using NHANES 2007-2018 and National Death Index linkage through December 31, 2019. Adults aged 20 to 79 years with CKM stages 1 to 4, estimated glomerular filtration rate of at least 15 mL/min/1.73 m2, complete activity data, no cancer history, and eligible follow-up were included. Baseline activity was classified as meeting or not meeting the guideline. Within-stage propensity-score weights were used in weighted Cox models. All-cause and cardiovascular mortality were the primary and secondary outcomes; 5-year risks used weighted survival curves, with competing-risk cumulative incidence also estimated for cardiovascular mortality. Results Among 19,654 participants, 1,190 all-cause deaths occurred during 134,037 person-years. Baseline attainment was associated with lower all-cause mortality overall (HR, 0.774; 95% CI, 0.675-0.888). Stage-specific HRs were 1.030, 0.803, 0.642, and 0.727 for stages 1 to 4, respectively; estimates were nonmonotonic. Five-year risk differences were +0.040, -0.830, -1.790, and -3.840 percentage points; only the stage 4 interval excluded the null. Cardiovascular mortality showed a similar overall cause-specific association (HR, 0.707; 95% CI, 0.547-0.914). Conclusions Observed baseline guideline attainment was associated with mortality in this observational target-trial emulation. The findings are consistent with current physical activity recommendations but do not estimate the effect of an activity-promotion intervention; prospective trials are needed to establish clinical benefit.

Discussion

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Cite This Study

Luo et al. (2026) conducted a cohort in Cardiovascular-kidney-metabolic (CKM) syndrome stages 1 to 4 (n=19,654). Baseline physical activity guideline attainment (≥150 min/week moderate-intensity, ≥75 min/week vigorous-intensity, or equivalent combination) vs. Not meeting baseline physical activity guidelines was evaluated on All-cause mortality (HR 0.774, 95% CI 0.675-0.888, p=.043 for interaction across CKM stages). Baseline physical activity guideline attainment was associated with lower all-cause mortality overall (HR 0.774, 95% CI 0.675-0.888) across CKM stages 1 to 4.

synapsesocial.com/papers/6ae8289b1eea7618b78899a5 https://doi.org/10.64898/2026.10.28.26366776

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Baseline Physical Activity Guideline Attainment and Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Baseline Physical Activity Guideline Attainment and Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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